Abacavir, is the International Nonproprietary Name (INN) of {(1S,4R)-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-cyclopent-2-enyl}methanol, and CAS No. 136470-78-5. Abacavir sulfate is a potent selective inhibitor of HIV-1 and HIV-2, and can be used in the treatment of human immunodeficiency virus (HIV) infection.
The structure of abacavir hemisulfate salt corresponds to formula (I):

EP 434450-A discloses certain 9-substituted-2-aminopurines including abacavir and its salts, methods for their preparation, and pharmaceutical compositions using these compounds.
Different preparation processes of abacavir are known in the art. In some of them abacavir is obtained starting from an appropriate pyrimidine compound, by a process comprising a coupling reaction of said compound or a later intermediate with a sugar analogue residue, a cyclisation to form the imidazole ring and the introduction of the cyclopropylamino group at the 6 position of the purine ring.
Several methods to perform the cyclisation of intermediates of abacavir are described in the art. According to EP 434450-A, the cyclisation of several intermediates of abacavir, including the following intermediates where R is cyclopropylamino or chloride,
is carried out using formic acid or a reactive formic acid derivative, optionally in the presence of a cosolvent and a strong anhydrous acid such as ethanesulfonic acid. There is not an specific example where the cyclisation is carried out in the presence of an anhydrous acid. Example 27 illustrates the cyclisation of (+)-(1R,4S)-cis-N-[4-chloro-5-formamido-6-{[4-(hydroxymethyl)-2-cyclopentene-1-yl]amino}-2-pyrimidinyl]isobutyramide, using triethyl orthoformate and concentratre aqueous hydrochloric acid, thereby the amino group at 5 position of the pyrimidine is hydrolysed and the compound is cyclised. The main disadvantage is the formation of several by-products, affecting the yield and the purity of the compound obtained.
EP 741710-A describes the cyclisation of the N-{2-amino-4-chloro-6-[(1R,4S)-4-(hydroxymethyl)cyclopent-2-enylamino]pyrimidin-5-yl}formamide of the following formula,
using the same cyclisation conditions as the previous patent application, i.e. triethyl orthoformate and concentrate hydrochloric acid.
The same authors of both patents applications state in a later publication (cf. S. M. Daluge et al., Nucleosides, Nucleotides & nucleic acids 2000, vol. 19, pp. 297-327) that the cyclisation of N-{2-amino-4-chloro-6-[(1R,4S)-4-(hydroxymethyl)cyclopent-2-enylamino]pyrimidin-5-yl}formamide, occurred smoothly in triethyl orthoformate and concentrated aqueous hydrochloric acid, but it could not be cyclised in ethyl orthoformate with anhydrous acids, e.g. ethanesulfonic acid, concentratred sulfuric acid, or anhydrous hydrochloric acid. According to this document, the rapid formation of the cyclic compound using concentrated aqueous hydrochloric acid suggests that the conformation of the starting material may be unfavourable for cyclisation and that the addition of water disrupt internal H-bonds and facilitate cyclisation.
WO 2005/023811 describes the cyclisation of [(1S,4R)-4-(2,5-diamino-6-chloropyrimidin-4-ylamino)cyclopent-2-enyl]methanol of the following formula,
using triethyl orthoformate and a catalytic amount of anhydrous or concentrated hydrochloric acid, being the cyclisation preferably carried out in an aprotic apolar solvent. Unlike the starting material of the patent applications mentioned above, in this case the amino groups at 2 and 5 position are not protected.
Despite the teaching of this prior art documents, the research of new cyclisation processes of intermediates of abacavir, in particular intermediates having the amino group at 2- and 5-position of the pyrimidine protected with an acyl group, is still an active field, since the known processes proceed with low yield and purity, as it has been pointed out above. Thus, the provision of a new process for the cyclisation of said intermediates of abacavir to give the purine structure is desirable.